Gold compounds of the cinchona alkaloids and their derivatives and method of manufacturing same



Patented Feb. 1, 1944 KALOIDS AND THEIR DERIVATIVES AND METHOD OFMANUFACTURING SAlVIE Albert Rothmann, Berlin-Charlottenburg, Germany,assignor, by mesne assignments, to Bare York, N. Y a corporationChemicals, Inc., New of New York No Drawing. Application November 18,1940, Serial No. 366,142. In Germany December 1,

8 Claims. (Cl. 260-284) My invention relates to therapeuticallyeffective gold compounds and to methods of manufacturing same.

Gold compounds have been already used for the treatment of chronicarthritis. It has been observed in this connection that the usefulnessof the compound is essentially dependent upon the way in which the goldis attached to the molecule. Of special therapeutic interest werechiefly those compounds showing a structure of the type R-S--Au, Rrepresenting an aliphatic, aromatic or heterocyclic rest. Best knownamong inorganic gold salts is gold sodium thiosulphate. So-called doublesalts with one organic component have been hitherto less used intherapeutics or were soon abandoned again.

It has nOW been found that one obtains gold double compounds which arevery effective against the disease mentioned above by convertingcinchona alkaloids or their derivatives and gold halides into doublesalts. With various cinchona alkaloids gold double salts have alreadybeen made, as for example with AllCls (ref. Liebigs Annalen der Chemie,vol. 129, p, 17, vol. 135, p. 338 and vol. 241, p. 265) all of themshowing the formula: cinchona alkaloid 2HCL2AuC13. They were prepared bydissolving the alkaloid in hydrochloric acid and adding gold trichloridein excess. On testing them they were found to produce irritation in thetissues.

Entirely n'on-irritative double salts are obtained, however, by mixingthe bases of the alkaloids or their derivatives dissolved in an organicsolvent, preferably in alcohol, with solutions of gold halides, as forinstance AuCls or AuClaHClAHaO in an organic solvent. In most cases theorganic double salts precipitate immediately or they may be precipitatedby adding ether or some other precipitant. They correspond to thegeneral formula chinchona alkaloid AuHals. They are distinguished bybeing non-irritative, non-poisonous and especially by their therapeuticaction in chronic joint diseases. Taking in account that gold doublesalts of nearly similar formula have not been found useful intherapeutics and only gold compounds with the gold being attached to themolecule by sulphur, are still being used, the new double compounds areof special importance.

The new double salts are insoluble in water and the usual organicsolvents but easily soluble in benzyl alcohol and in a mixture of thelatter with vegetable oils.

Examples (1) 3.2 grams quinine dissolved in 20 ccms.

methanol is mixed with 4.1 grams AuClaHClAI-IzO dissolved in 20 ccms.methanol. After a short time there precipitates the gold double saltC20I-I24O2NaAuC13. It is sucked off and dried. Melting point Mil-152 C.(under decomposition).

A similar compound is obtained by using 3 grams -.AuCl3.

(2) Corresponding to Example 1 a gold double salt is obtained withquinidine, having a melting point of 158.

(3) Out of 1.2 grams acetyl quinine and 1.3 grams AuCla.HCl.4I-Iz0, eachdissolved in 10-15 ccms. methanol and mixed, results a double salt ofthe formula: C22H2603N2.AU.C13. When separating ofi it is somewhat oilybut on rubbing and cooling on ice it gradually becomes solid. It meltsunder decomposition at 162-163 C.

(4) To 2.26 grams hydro-iodo-quinine, dissolved in 30 ccms. of absoluteethyl alcohol, 2.1 grams AuClaHClAI-IzO, dissolved in alcohol, areadded. The double salt precipitates immediately. It is yellow and meltsunder sintering and decomposition at 142-144. C.

(5) 1.1 grams hydro-quinine and 1.0 gram AuClaHClAI-IzO are eachdissolved in 10 grams of acetone and mixed. By adding ether the yellowcolored double salt is precipitated. It darkens at about 139 C. andmelts under sintering and decomposition at 183 C.

(6) 1.3 grams dimethylaminoethylhydrocupreine are dissolved in 8 ccms.methanol and mixedwith a olution of 1.4 grams AuClaI-ICl/lHzO in 5 ccms.methanol. The resulting double salt is oily; by adding some ether andcooling on ice it gradually turns solid, At 86 C. it starts decomposing.

(7 To a solution of 1.1 grams quinine in 10 ccms. chloroform is added 2grams AllBl3.HBr.51-I2O dissolved in 10 ccms. chloroform with 0.5 ccm.ether. By adding petroleum ether an oil separates off which afterdecanting and treating with petroleum ether gradually becomes solid. Thedark red colored product melts after sintering and under decompositionat -176 C.

By cinchona alkaloids in my specification and claims I mean cinchonaalkaloid bases such as quinine, quinidine, acetyl quinine,hydroiodoquinine, hydro-quinine and dimethyl-amino-ethylhydrocupreine.

Various changes may be made in the details disclosed in the foregoingspecification without departing from the invention or sacrificing theadvantages thereof.

In the claims affixed to this specification no selection of anyparticular modification of the invention is intended to the exclusion ofother modifications thereof, and the right to subsequently make claim toany modification not covered by these claims is expressly reserved.

I claim:

1. Double gold-halide salts of cinchona alkaloids of the formulacinchona. alkaloid AuHaIi; said salts being precipitated in solid formand the salt portion thereof being free of acid substituents, said saltsbeing prepared as a therapeutic.

2. A double gold-chloride salt of a cinchona alkaloid having the formulaC2oH24O2N2'AuC13, said salt being precipitated in solid form and thebeing precipitated in solid form and the salt portion thereof being freeof acid substituents, said salt being prepared as a therapeutic.

5. The process of producing therapeutically effective double gold-halidesalts of cinchona alkaloids which comprises reacting a gold halide with7 a cinchona alkaloid in the presence of an organic salt portion thereofbeing free of acid substituents, said salt being prepared as atherapeutic.

3. A double gold-chloride salt of acetyl quinine having the formulaCzzHzsOaNz-Cls, said salt being precipitated in solid form and the saltportion thereof being free of acid substituents, said salt beingprepared as a therapeutic.

4. A double gold-chloride salt of hydro-quinine hailing the formulaC20H2sO2N2'AuC13, said Salt solvent.

6. The process of producing therapeutically efiective double gold-halidesalts of cinchona alkaloids which comprises reacting a gold-halide witha cinchona alkaloid in the presence of a

